Table 2. Maximal percentage of inhibition of IL-8, MMP-9, GM-CSF and IL-1β release from neutrophils of healthy subjects and COPD patients.
| Cytokine | Healthy | COPD | ||||
|---|---|---|---|---|---|---|
| IL-8 | Maximal % Inhibition |
-log IC50 | N | Maximal % Inhibition |
-log IC50 | N |
| AZD8999 | 46.5 ± 2.5 | 8.2 ± 0.2 | 5 | 50.5 ± 1.9 | 10.3± 0.2* | 5 |
| Fluti | 117 ± 4.4# | 7.8 ± 0.1 | 5 | 57.2 ± 3.3* | 7.4± 0.14# | 5 |
| MMP9 | Maximal % Inhibition |
-log IC50 | N | Maximal % Inhibition |
-log IC50 | N |
| AZD8999 | 77.7 ± 2.6 | 8.1 ± 0.1 | 5 | 62.9 ± 2 | 10 ± 0.1* | 5 |
| Fluti | 95.3 ± 3.3# | 8.5 ± 0.16 | 5 | 60 ± 3* | 7.7 ± 0.12*# | 5 |
| IL-1β | Maximal % Inhibition |
-log IC50 | N | Maximal % Inhibition |
-log IC50 | N |
| AZD8999 | 39 ± 2.4 | 10.3 ± 0.3 | 3 | 27.5 ± 4 | 7 ± 1.8* | 4 |
| Fluti | 75.6 ± 1.6# | 10.4 ± 0.23 | 3 | 61.7 ± 3* | 8.3 ± 0.17* | 4 |
| GM-CSF | Maximal % Inhibition |
-log IC50 | N | Maximal % Inhibition |
-log IC50 | N |
| AZD8999 | 0 | ND | 4 | 73.4 ± 5* | 6.8 ± 0.15 | 4 |
| Fluti | 82.7 ± 3.6 | 8 ± 0.13 | 4 | 19.6 ± 3.3* | 7.4 ± 0.4 | 4 |
Neutrophils were incubated with AZD8999 (0.1nM-1μM) or fluticasone (Fluti; 0.1nM-1μM) for 1h and stimulated with lipopolysaccharide (LPS 1μg/ml) for 6 h. The levels of different cytokines in the cell supernatant were determined and the maximal % of inhibitions were calculated. Values are mean ± SD of 3–5 independent donor experiments run in triplicate. IC50 values for half-maximum inhibition were calculated by nonlinear regression analysis.
*p < 0.05 vs Healthy values
#p<0.05 vs AZD8999 group.
ND: not determined.